miRNA as therapeutic targets of pancreatic cancer

Coordinator:		Prof. Dr. med Stephan Hahn
Institution:		Ruhr-Universität Bochum, Molekulare Gastroenterologische Onkologie (MGO)
Homepage:		www.rub.de/mgo

Recently, microRNAs (miRNAs), a novel class of 18-23 nt long non-coding RNAs, have gained attention as another family of molecules involved in cancer development. Upon binding to their target RNAs, miRNAs cause posttranscriptional gene silencing by either cleaving the target mRNA or by inhibiting the translation process. Due to their high stability even in poorly preserved specimen, miRNAs are expected to be robust clinical analytes, valuable for clinical research and biomarker discovery. By virtue of their apparent role in tumorigenesis, miRNAs may not only be potential targets for new prognostic and diagnostic strategies but also have therapeutic potential. Within this project we were able to generate the first cell type specific miRNome for pancreatic normal and acinar cells, for pancreatic carcinoma cells and for chronic pancreatitis. From the altogether 78 miRNAs identified to be differentially expressed between normal and cancer cells, 15 miRNAs were identified as potential novel biomarker and therapy candidates. Subsequently, we found that miR-135b is able to distinguish with excellent sensitivity and specificity between non-cancerous and cancerous tissue from the pancreas, and can thus be used as a tissue based biomarker for the diagnosis of pancreatic carcinoma. In addition, miR-1246 (recently reclassified as RNU2-1f) was shown to be able to help to discover patients with pancreatic cancer in a blood based assay (here serum). Lastly, a novel organometallic rhenium based bio-conjugate with favorable properties for bioimaging and applicability  in solid-phase peptide synthesis was discovered, which can be used not only for imaging but may also help to facilitate cellular uptake of therapeutic molecules.